This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective To evaluate the protective effects of the traditional Chinese medicine formula Shenxiankang on renal injury and fibrosis,and to explore its potential mechanisms of action.Methods Chronic kidney disease(CKD)model was established in mice using unilateral ureteral obstruction(UUO).The mice were randomly divided into four groups:sham,UUO,and Shenxiankang(SXK)Low/High dose groups(1500,4500 mg/(kg·d)),each comprising eight mice.The each SXK groups received daily oral administration of Shenxiankang,and the remaining mice were gavaged equivalent volumes of saline for 7 d.After the experiment,renal tissues were collected for assessment of renal injury and fibrosis using HE and Masson staining.The expression levels of fibrosis markers and proteins involved in the epithelial membrane protein 3(Emp3)and Tgf-β/Smad3 signaling pathway were determined by Real-time PCR,immunohistochemistry,and Western Blot.In cell-based experiments,the effects of Shenxiankang on the Emp3/Tgf-β/Smad3 pathway and its interaction with TGF-beta receptor R2(Tgfβ2)were further analyzed using an Emp3 knockdown and Co-IP assays.Results Shenxiankang significantly reduced immune cell infiltration and tubular atrophy in the UUO model group and decreased the expression of kidney injury markers kidney injury molecule 1(Kim1)and Lipocalin 2(Lcn2),confirming its efficacy in alleviating renal injury.Masson staining and analysis of fibrosis markers Fibronectin(Fn)and α-smooth muscle actin(α-SMA)indicated that Shenxiankang effectively suppressed fibrosis induced by UUO.Mechanistic studies revealed that Shenxiankang exerted its effects by selectively downregulating the abnormal activation of the Emp3/Tgf-β/Smad3 signaling pathway,a finding further supported by cellular experiments showing that Shenxiankang modulates Tgf-β/Smad3 signaling through Emp3 regulation.Moreover,the Co-IP experiment result indicate that Shenxiankang exerts its effects by regulating the interaction between Emp3 and Tgfβ2.Conclusions Shenxiankang exhibits significant protective effects in a mouse model of chronic kidney disease,effectively reducing renal injury and fibrosis.These effects are likely mediated through the downregulation of the Emp3/Tgf-β/Smad3 signaling pathway,suggesting Shenxiankang's potential therapeutic value in renal protection.

Objective To evaluate the protective effects of the traditional Chinese medicine formula Shenxiankang on renal injury and fibrosis,and to explore its potential mechanisms of action.Methods Chronic kidney disease(CKD)model was established in mice using unilateral ureteral obstruction(UUO).The mice were randomly divided into four groups:sham,UUO,and Shenxiankang(SXK)Low/High dose groups(1500,4500 mg/(kg·d)),each comprising eight mice.The each SXK groups received daily oral administration of Shenxiankang,and the remaining mice were gavaged equivalent volumes of saline for 7 d.After the experiment,renal tissues were collected for assessment of renal injury and fibrosis using HE and Masson staining.The expression levels of fibrosis markers and proteins involved in the epithelial membrane protein 3(Emp3)and Tgf-β/Smad3 signaling pathway were determined by Real-time PCR,immunohistochemistry,and Western Blot.In cell-based experiments,the effects of Shenxiankang on the Emp3/Tgf-β/Smad3 pathway and its interaction with TGF-beta receptor R2(Tgfβ2)were further analyzed using an Emp3 knockdown and Co-IP assays.Results Shenxiankang significantly reduced immune cell infiltration and tubular atrophy in the UUO model group and decreased the expression of kidney injury markers kidney injury molecule 1(Kim1)and Lipocalin 2(Lcn2),confirming its efficacy in alleviating renal injury.Masson staining and analysis of fibrosis markers Fibronectin(Fn)and α-smooth muscle actin(α-SMA)indicated that Shenxiankang effectively suppressed fibrosis induced by UUO.Mechanistic studies revealed that Shenxiankang exerted its effects by selectively downregulating the abnormal activation of the Emp3/Tgf-β/Smad3 signaling pathway,a finding further supported by cellular experiments showing that Shenxiankang modulates Tgf-β/Smad3 signaling through Emp3 regulation.Moreover,the Co-IP experiment result indicate that Shenxiankang exerts its effects by regulating the interaction between Emp3 and Tgfβ2.Conclusions Shenxiankang exhibits significant protective effects in a mouse model of chronic kidney disease,effectively reducing renal injury and fibrosis.These effects are likely mediated through the downregulation of the Emp3/Tgf-β/Smad3 signaling pathway,suggesting Shenxiankang's potential therapeutic value in renal protection.

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

Objective To investigate the expression of inositol polyphosphate 4-phosphatase type Ⅱ B(INPP4B)in colorectal cancer(CRC)and the relevant clinical significance,to determine the relationship between INPP4B and matrix metallopeptidase 7(MMP7)in CRC cells,and to make preliminary exploration of the effects of INPP4B on the proliferation and migration of CRC cells and mechanisms involved.Methods The TIMER2.0 and GEPIA2 databases were used to analyze the differences in INPP4B expression between cancer and para-cancerous tissues and the effects of such differences on the prognosis of CRC.The expression of INPP4B in 102 surgically resected CRC tumors was determined by immunohistochemistry(IHC),and the correlation between INPP4B and clinical pathological indicators was analyzed.In CRC cells with overexpressed/knocked-down INPP4B,the expression of INPP4B and MMP7 were examined by real time fluorogenic quantitative PCR,the protein expression of INPP4B was assessed by Western blot,cell proliferation was determined using the CellTiter 96? AQueous One assay,and cell migration and invasion were assessed using wound healing assay and real-time label-free dynamic cell analysis(RTCA).The LinkedOmics database was used to analyze signaling pathways related to INPP4B function,and the role of potential key molecules was validated at the cellular level.Results Analysis with the TIMER2.0 database and GEPIA2 database showed elevated INPP4B expression(colon adenocarcinoma[COAD]:2.30,rectal adenocarcinoma[READ]:2.33)in CRC compared to normal tissue(COAD:1.91,READ:1.89).IHC testing confirmed that INPP4B was upregulated in clinical CRC tissues and paracancerous tissues(P＜0.001).Cox regression model analysis showed that INPP4B(hazards ratio[HR]=1.457,95％confidence interval[CI]:1.003-2.115)affected the prognosis of CRC,and the Kaplan-Meier curve showed that patients with high INPP4B expression had shorter overall survival(P＜0.05).x2 test was performed to analyze the relationship between INPP4B expression and clinicopathological indexes,and it was found that high expression of INPP4B was correlated with lymph node metastasis(x2=3.997,P=0.046)and neural invasion(x2=8.511,P=0.004).In in vitro experiments,CRC cells overexpressing INPP4B showed a significantly increased cell proliferation and migration compared to the cells in the control group(P＜0.05).Analysis using the LinkedOmics database showed that INPP4B was correlated with extracellular matrix remodeling and cell migration.Pearson's correlation analysis showed that MMP7 was positively correlated with INPP4B(r=0.3782,P＜0.001).INPP4B overexpression or knockdown in vitro also led to the upregulation or the downregulation of MMP7 expression in CRC cells.Conclusion INPP4B is highly expressed in CRC tissues and significantly correlated with lymph node metastasis,neural invasion,and patient prognosis.MMP7 may mediate the role of INPP4B in promoting CRC cell migration and invasion.

Objective:To construct the evaluation system of Intensive Care Unit (ICU) practice base for master of nursing specialist.Methods:The evaluation indicators at all levels were initially formulated through literature review and semi-structured interviews. Using the sampling method, 25 experts were selected from August to October 2021 for correspondence. The evaluation system of ICU practice base for master of nursing specialist was finally determined by Delphi method and analytic hierarchy process.Results:A total of two rounds of consultation were conducted. The expert positive coefficients were 88% (22/25) and 91% (20/22), the expert authority coefficients were 0.953 and 0.948, and the Kendall's W were 0.211 and 0.210 respectively with statistical differences ( P<0.01). The final evaluation system of ICU practice base for master of nursing specialist included 4 first-level indicators, 15 second-level indicators and 103 third-level indicators and evaluation contents. Conclusions:The evaluation system of ICU practice base for master of nursing specialist is scientific, reliable and comprehensive, which can provide reference for formulating the evaluation criteria of clinical practice base for nursing graduate students.

Objective:To investigate vision-related quality of life, anxiety and depression in patients with primary angle-closure glaucoma (PACG) and the influencing factors in Baotou, Inner Mongolia.Methods:A cross-sectional study was conducted.One hundred and eighty-two consecutive PACG patients (364 eyes) with intraocular pressure ≤20 mmHg (1 mmHg=0.133 kPa) at 3 random times after treatment were enrolled in Baotou Chaoju Ophthalmic Hospital from September 2018 to January 2020.Gender, age, marital status, education level, monthly income, total treatment cost, glaucoma treatment time, surgery and drug treatment history, best corrected visual acuity (BCVA), Humphrey visual field index (VFI) and scores of the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) and Hospital Anxiety and Depression Scale (HADS) of patients were recorded.Pearson correlation analysis was used to analyze the correlation between age and composite VFQ-25 score.Spearman rank correlation analysis was used to analyze the correlation between other statistical data.Stepwise multivariate linear regression was used to analyze the correlation between composite VFQ-25 score, HADS score and statistically significant influencing factors above.This study protocol adhered to the Declaration of Helsinki, and was approved by an Ethics Committee of Beijing Tongren Hospital, Capital Medical University (No.TRECKY2015-30). Written informed consent was obtained from each subject.Results:The mean age of subjects was (59.75±8.43) years.The mean composite VFQ-25 score was (68.59±14.43) points.The mean HADS, HADS-Anxiety (HADS-A) and HADS-Depression (HADS-D) scores were 16.00 (12.00, 20.00), 8.00 (6.00, 10.00), 8.00 (6.00, 10.00) points, respectively.The proportion of anxious (HADS-A score>10 points) and depressd (HADS-D score >10 points) patients was 18.1% (33/182) and 13.7% (25/182), respectively.Age was positively correlated with BCVA in eyes with better and worse vision ( rs=0.36, 0.29; both at P<0.01), and it was negatively correlated with mean deviation (MD) of Humphrey visual field in the better-MD and worse-MD eyes, VFI of Humphrey visual field in the better-VFI and worse-VFI eyes ( rs=-0.21, -0.23, -0.30, -0.23; all at P<0.01). The composite VFQ-25 score was negatively correlated with age, BCVA in the eyes with better and worse vision ( rs=-0.32, -0.34, -0.48; all at P<0.01), and it was positively correlated with MD in the better-MD and worse-MD eyes, VFI in the better-VFI and worse-VFI eyes ( rs=0.37, 0.45, 0.38, 0.46; all at P<0.01). The HADS-A score was negatively correlated with MD in the better-MD eye ( rs=-0.20, P<0.01). The HADS-D score was positively correlated with BCVA in the eyes with worse vision ( rs=0.26, P<0.01) and negatively correlated with MD in the better-MD and worse-MD eyes, and VFI in the worse-VFI eyes ( rs=-0.21, -0.22, -0.22; all at P<0.01). The HADS score was positively correlated with BCVA in the eyes with worse vision ( rs=0.22, P<0.01), and negatively correlated with MD in the better-MD and worse-MD eyes, and VFI in the worse-VFI eyes ( rs=-0.20, -0.20, -0.21; all at P<0.01). The composite VFQ-25 score was negatively correlated with mean HADS-A, HADS-D and HADS scores ( rs=-0.41, -0.41, -0.45; all at P<0.01). According to the multivariate analysis, the composite VFQ-25 score was related to age ( P<0.01), education level ( P<0.01), total treatment cost ( P<0.05), BCVA in the eyes with better vision ( P<0.05) and MD in the worse-MD eyes ( P<0.01). The HADS score was related to gender ( P<0.05) and the composite VFQ-25 score ( P<0.01). Conclusions:The vision-related quality of life and incidence of anxiety and depression are low in patients with PACG in Baotou region, Inner Mongolia.With age increasing, PACG patients suffer from declined visual function, increased visual field damage, reduced vision-related quality of life and raised anxiety and depression.The vision-related quality of life is poorer in patients with lower education level and higher total treatment cost.Female glaucoma patients are more likely to suffer from anxiety and depression.

Objective? To explore how to apply best practice guideline in teaching and the initial effects. Methods? After deeply investigating courses, this study selected best practice guideline by combining with existing problems in teaching. Combined with the first-level and second-level class, a careful design scheme was conducted by each course groups and multiple rounds of project argumentation. After determining the program and teaching resources, each guideline application course group began to fully implement according to their own program. Results? The best practice guidelines were successfully applied in 7 courses through various teaching forms including situation simulation, flipped classroom, case teaching as well as role playing which played an positive role in teaching content, teaching design and teaching evaluation. Conclusions? In the whole process of implementation, teachers and students feel that the application of best practice guideline in nursing teaching is helpful to expand the frontier content of teaching, establish the evidence-based concept of teachers and students and initially cultivate critical thinking. It also plays a positive role in arousing the enthusiasm of nursing students and the comprehensive application of the knowledge they have learned. It makes evaluation methods flexible and diversified and is also beneficial to the real and objective response to the learning effect of nursing students.

OBJECTIVE To investigate the effect of diallyl sulfide (DAS) in protection against acute lung injury in rats induced by paraquat(PQ). METHODS A total of 100 male Wistar rats were randomly divided into normal control group,PQ 70 mg·kg-1 model group,and DAS 25,50 and 100 mg·kg-1 treatment groups,with 20 rats in each group. A poisoning model was estalolished after administration ig at a single dose of PQ 70 mg·kg-1,while the normal control group was ip given the same volume of normal saline. DAS 25,50 and 100 mg · kg-1 was intraperitoneally injected 30 min before and after PQ exposure. Five rats in each group were sacrificed at 1,3,6 and 12 h,respectively. The inferior lobe of the right lung was observed by HE staining under an optical microscope. Tissue of the upper lobe of the right lung was used to detect the content of nitric oxide (NO). Alveolar macrophages (AMs) were collected and cultured for 24 h,and the content of nitric oxide synthase(iNOS)in the supernatant was detected. AMs were cultured for 72 h and the expression of iNOS protein in AMs was detected by immunocytochemistry method. RESULTS Compared with normal control group,the alveolar structure of PQ group was severely damaged and the pathological score was significantly increased(P<0.01). The NO content of PQ group was significantly higher than in normal control group(P<0.01). The content and protein expression of iNOS were significantly increased in PQ group(P<0.01). Compared with PQ group,the lung injury score of rats in DAS 50 mg·kg-1 group at 3,6 and 12 h and in the DAS 100 mg·kg-1 group at each time point was decreased(P<0.05). Compared with PQ group,the NO content of DAS 25 and 50 mg · kg-1 group was decreased(P<0.05),and the NO content of DAS 100 mg · kg-1 group was significantly reduced(P<0.01). The content of iNOS was reduced in DAS 100 mg · kg-1 group(P<0.05). Compared with PQ group,the expression of iNOS protein in DAS groups was decreased(P<0.05). CONCLUSION DAS can inhibit the oxidative damage in rats induced by PQ.